Porphyromonas gingivalis is a Gram-negative bacterium associated with human adult periodontal disease. The oral cavities of mice can be infected with P. gingivalis, and such oral infection induces alveolar bone loss, a sequela of periodontal disease. Oral infection may also induce other immunologically-based diseases. The mouse offers an extremely versatile model for the study of the host immune response to P. gingivalis. The murine immune system has been well-characterized and strains with narrowly specific, genetically defined immunodeficiencies have been developed. The requirement for various aspects of the host immune system in the protection from or initiation and progression of alveolar bone loss by P. gingivalis will be determined by measuring bone loss in infected and uninfected mice with specific immunodeficiencies. Localized oral infection may produce antigen specific or nonspecific immune stimulation, which may result in peripheral effects including serum antibody, cytokines, expansion of some immune cell populations and alteration of surface antigen expression. The capacity of P. gingivalis to produce peripheral host responses in vivo will be defined by flow cytometry of splenocytes after oral infection of mice. Bacterial induction of cytokines could amplify the effects of lymphocytes partially activated by unrelated antigens. This hypothesis will be tested using congenic strains of mice which develop a cytotoxic T lymphocyte response to donor cell bearing a minor histocompatibility antigen only when they receive "help" from a second stimulus. Preliminary data suggest that this second stimulus may be provided by oral infection with P. gingivalis, thus P. gingivalis might contribute to graft versus host disease. These studies will thus examine the host response leading to or inhibiting alveolar bone loss and will begin to elucidate the relationship between local oral infection and systemic effects in the host. Development of this murine oral infection model will be useful in the future for clarifying the interaction between two unrelated immune responses. Such clarification is likely to produce new avenues of investigation of disease etiology.